Another Anti-CD20 Monoclonal in Clinical Trials

Anti-CD20 monoclonals are all the rage these days. Notwithstanding the recent adverse effects reports, Rituxan is the single most crucial discovery in the last decade for CLL patients. We’re keeping our fingers crossed that the FDA will approve the next in line contender for the anti-CD20 crown HuMax-CD20.

Cripes, it takes so darn long for new inventions to go through the clinical trials and regulatory process before we can hope to see them commercially available! Sometimes we get discouraged by the snails’ pace. All the same, if we don’t stoke the research and drug testing pipeline with new candidates, we will never get new and improved drugs. If not us, those of our children unlucky enough to get this familial cancer will benefit from the research we support now.

Today we would like to bring to your attention a new clinical trial testing another new anti-CD20 monoclonal in CLL and NHL patients. Never heard of veltuzumab? You are not alone. Here is the skinny on this new drug:

“Veltuzumab” is made by a company called Immunomedics. It used to be called IMMU-160 back when it was still being tested in the lab and had not made it into clinical trials, so don’t get flummoxed if you see that handle rather than veltuzumab in some of the press releases and articles.

This is an early phase trial, and they hope to recruit a total of 72 patients, a mix of treated and untreated CLL and NHL patients. The study started in January of 2008, but I know that they are still recruiting.

The trial is offered at a number of sites, and you might find one close to home: Savannah, Georgia; Denville, New Jersey; Morristown, New Jersey; New York City; New Hyde Park; Lemoyne, Pennsylvania. I highlighted the LIJ recruitment site because that is home to Dr Kanti Rai, one of our best-known research experts.

This clinical trial is a dose escalation study, intended to identify the safe and effective dose of this new monoclonal antibody. Patients will be divided into three cohorts, depending on when they enrolled in the study. The dosage of the drug will be escalated from 40mg to 80mg to 160mg in the three cohorts. Compared to the “standard” dose of 375 mg/m2 of Rituxan used most often, it appears veltuzumab requires smaller amounts of the drug.

Patients will get veltuzumab as subcutaneous shots on alternate weeks, for a total of 4 injections, on alternate weeks. By way of comparison, Rituxan is usually given as an intravenous infusion. That is unless you are a devotee of Prof. Taylor’s concept of CD20 Shaving and therefore sweet-talked your oncologist to provide you with microdoses of Rituxan as subcutaneous injections. Prof. Taylor makes a strong case for using much smaller amounts of Rituxan in order to avoid the shaving reaction. We were sufficiently impressed by the science that we funded his research with your donated dollars.

Here is the link to the official citation for the new veltuzumab clinical trial where you can find more information: http://clinicaltrials.gov/ct2/show/NCT00546793. It has phone numbers and contact information if you want to get additional information.

Much of the logic for using veltuzumab comes from the first study where this drug was given as weekly intravenous infusions to NHL patients. It showed good tolerability and even some level of efficiency at weekly intravenous doses as low as 80-120 mg/m2 over four consecutive weeks. These clinical results confirmed lab studies using cells followed by mice studies.

What makes veltuzumab worth studying?

Our beloved Rituxan is a chimeric antibody, meaning it has both human and mouse protein in it. It is generally thought that a chimeric antibody is better than a full mouse antibody since it is less likely to provoke an acute immune response and infusion-related adverse effects. Using the same logic, a fully human or humanized monoclonal antibody (such as HuMax-CD20 and veltuzumab) is likely to be even better than the chimeric versions.

While the chimeric nature of Rituxan has not posed insurmountable problems, it may be an advantage to have more completely human antibodies. This is especially so if repeated injections may be desired in patients. In recent years we have begun to see the use of Rituxan in treating autoimmune diseases such as AIHA and ITP, even rheumatoid arthritis and Lupus.

These patients are likely to be on maintenance administration of Rituxan over many years, and in those circumstances, it is far preferable if the antibody used is fully human, with no smidgen of mouse protein to create over-the-top immune reactions with repeated administration of the drug. The lower drug dose and the potential for reduced infusion-related adverse effects are among the possible benefits of veltuzumab.

Also, if the veltuzumab can be given as a quick jab in the arm, rather than sitting in one of those uncomfortable reclining chairs in the back room while Rituxan does its slow drip-drip-drip act over several hours, we can see how that would be more cost-effective and efficient.